Intercalary Allograft Reconstruction of the Proximal Tibia With and Without a Free Fibula Flap in Pediatric Patients.

BACKGROUND: Limb salvage of the proximal tibia can be difficult due to the growth potential of and functional demands of the pediatric patients. Multiple reconstruction techniques exist, however, the ideal form of reconstruction is yet to be elucidated. The purpose of the current study is to evaluate outcomes in patients with an intercalary resection of the proximal tibia reconstructed with an allograft with or without a free vascularized fibula flap (FVF). METHODS: Seventeen pediatric patients (9 males, 8 females) underwent lower extremity limb salvage with the use of intercalary cadaveric allograft at a mean age of 12±4 years. The most common diagnoses were osteosarcoma (n=6) and Ewing sarcoma (n=6). Patients were reconstructed with an allograft alone (n=6) or supplemented with an FVF (n=11). RESULTS: All surviving patients had at least 2 years of clinical follow-up, with the mean follow-up of 12±7 years. The mean time to union of the allograft was 11±4 months, with 6 patients requiring additional bone grafting. There was no difference in the need for an additional bone graft (odds ratio=1.14, P=1.0) between patients with an FVF and those without. Four patients underwent an amputation, all with an allograft alone, due to disease recurrence (n=2) and due to infection (n=2). As such, there was a higher 10-year overall limb-salvage rate when the allograft was combined with an FVF compared with an allograft alone (100% vs. 33%, P=0.001). At last follow-up, the mean Mankin and Musculoskeletal Tumor Society rating was 86%, with a higher mean score in patients reconstructed with an FVF (94% vs. 70%, P=0.002). CONCLUSION: Use of an intercalary allograft supplemented with an FVF to reconstruct the proximal tibia provides a durable means of reconstruction with an excellent functional outcome following oncologic proximal tibia resection in a pediatric population. LEVEL OF EVIDENCE: Level III-therapeutic level.

Osteosarcoma: a comprehensive review.

Osteosarcoma (OS) is a relatively rare tumor of bone with a worldwide incidence of 3.4 cases per million people per year. For most of the twentieth century, five-year survival rates for classic OS were very low. In the 1970s, the introduction of adjuvant chemotherapy in the treatment of OS increased survival rates dramatically. The current article reviews the various types of OS and analyzes the clinical and histological features. We also examine historical and current literature to present a succinct review of methods for diagnosis and staging, as well as treatment, and we also discuss some of the future directions of treatment.

Defining the "Three-Dimensional Sagittal Plane" in Thoracic Adolescent Idiopathic Scoliosis.

BACKGROUND: Obtaining accurate measurements of scoliosis from two-dimensional (2-D) radiographs can be challenging because of the three-dimensional (3-D) nature of the deformity. Previous studies have shown that the sagittal plane, in particular, is misrepresented on 2-D radiographs because of the influence of axial plane rotation. The purpose of the current study was to define a methodology for measuring the 3-D segmental sagittal alignment of the spine in patients with adolescent idiopathic scoliosis (AIS) and to assess the effect of axial plane rotation on differences between 3-D and 2-D measures of deformity. METHODS: Preoperative and postoperative EOS images of 120 consecutive patients with AIS (primary thoracic curves) treated with segmental thoracic pedicle-screw instrumentation were analyzed in the "3-D sagittal plane." The technique measured 3-D kyphosis or lordosis in the specific plane of sagittal motion for each spinal motion segment. The kyphosis (+) and lordosis (-) values of the segments from T5 to T12 were summed to give the 3-D measurement of T5-T12 kyphosis. These values were compared with the standard 2-D measurements of T5-T12 kyphosis on lateral radiographs, and a correlation analysis with regard to axial plane rotation of the apex was performed. RESULTS: The average age (and standard deviation) of the patients was 14 ± 2 years. The mean preoperative Cobb angle on the standard 2-D view was 55° ± 10° and on the 3-D view was 52° ± 9° (p ≤ 0.001). On the 3-D view, the mean preoperative T5-T12 kyphosis was 6° ± 14°, and the kyphosis significantly increased to 26° ± 6° postoperatively (p < 0.001). The T5-T12 kyphosis on the standard 2-D view measured 18° ± 13° preoperatively and 27° ± 6° postoperatively (p < 0.001). The difference between the 2-D and 3-D measurements of T5-T12 kyphosis strongly correlated with apical vertebral rotation (r = 0.85; p < 0.01). CONCLUSIONS: Routine 2-D measurements of thoracic kyphosis erroneously underestimate the preoperative loss of kyphosis in AIS because of errors associated with axial plane rotation, an inherent component of thoracic scoliosis.

Biomechanical Evaluation of Plate Versus Lag Screw Only Fixation of Distal Fibula Fractures.

Traditional fixation of unstable Orthopaedic Trauma Association type B/C ankle fractures consists of a lag screw and a lateral or posterolateral neutralization plate. Several studies have demonstrated the clinical success of lag screw only fixation; however, to date no biomechanical comparison of the different constructs has been performed. The purpose of the present study was to evaluate the biomechanical strength of these different constructs. Osteotomies were created in 40 Sawbones(®) distal fibulas and reduced using 1 bicortical 3.5-mm stainless steel lag screw, 2 bicortical 3.5-mm lag screws, 3 bicortical 3.5-mm lag screws, or a single 3.5-mm lag screw coupled with a stainless steel neutralization plate with 3 proximal cortical and 3 distal cancellous screws. The constructs were tested to determine the stiffness in lateral bending and rotation and failure torque. No significant differences in lateral bending or rotational stiffness were detected between the osteotomies fixed with 3 lag screws and a plate. Constructs fixed with 1 lag screw were weaker for both lateral bending and rotational stiffness. Osteotomies fixed with 2 lag screws were weaker in lateral bending only. No significant differences were found in the failure torque. Compared with lag screw only fixation, plate fixation requires larger incisions and increased costs and is more likely to require follow-up surgery. Despite the published clinical success of treating simple Orthopaedic Trauma Association B/C fractures with lag screw only fixation, many surgeons still have concerns about stability. For noncomminuted, long oblique distal fibula fractures, lag screw only fixation techniques offer construct stiffness similar to that of traditional plate and lag screw fixation.

Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity.

NLRP3 nucleates the inflammasome, a protein complex responsible for cleavage of prointerleukin-1beta (IL-1beta) to its active form. Mutations in the NLRP3 gene cause the autoinflammatory disease spectrum cryopyrin-associated periodic syndromes (CAPS). The central role of IL-1beta in CAPS is supported by the response to IL-1-targeted therapy. We developed two Nlrp3 mutant knockin mouse strains to model CAPS to examine the role of other inflammatory mediators and adaptive immune responses in an innate immune-driven disease. These mice had systemic inflammation and poor growth, similar to some human CAPS patients, and demonstrated early mortality, primarily mediated by myeloid cells. Mating these mutant mice to various gene mutant backgrounds showed that the mouse disease phenotype required an intact inflammasome, was only partially dependent on IL-1beta, and was independent of T cells. These data suggest that CAPS are true inflammasome-mediated diseases and provide insight for more common inflammatory disorders.

NLRP3/cryopyrin is necessary for interleukin-1beta (IL-1beta) release in response to hyaluronan, an endogenous trigger of inflammation in response to injury.

Inflammation under sterile conditions is a key event in autoimmunity and following trauma. Hyaluronan, a glycosaminoglycan released from the extracellular matrix after injury, acts as an endogenous signal of trauma and can trigger chemokine release in injured tissue. Here, we investigated whether NLRP3/cryopyrin, a component of the inflammasome, participates in the inflammatory response to injury or the cytokine response to hyaluronan. Mice with a targeted deletion in cryopyrin showed a normal increase in Cxcl2 in response to sterile injuries but had decreased inflammation and release of interleukin-1beta (IL-1beta). Similarly, the addition of hyaluronan to macrophages derived from cryopyrin-deficient mice increased release of Cxcl2 but did not increase IL-1beta release. To define the mechanism of hyaluronan-mediated activation of cryopyrin, elements of the hyaluronan recognition process were studied in detail. IL-1beta release was inhibited in peritoneal macrophages derived from CD44-deficient mice, in an MH-S macrophage cell line treated with antibodies to CD44, or by inhibitors of lysosome function. The requirement for CD44 binding and hyaluronan internalization could be bypassed by intracellular administration of hyaluronan oligosaccharides (10-18-mer) in lipopolysaccharide-primed macrophages. Therefore, the action of CD44 and subsequent hyaluronan catabolism trigger the intracellular cryopyrin --> IL-1beta pathway. These findings support the hypothesis that hyaluronan works through IL-1beta and the cryopyrin system to signal sterile inflammation.

Monocytes from familial cold autoinflammatory syndrome patients are activated by mild hypothermia.

BACKGROUND: Familial cold autoinflammatory syndrome (FCAS) is characterized by rash, fever, and arthralgia in response to cold exposure. CIAS1, the gene that codes for cryopyrin, is mutated in FCAS. Treatment with anakinra (IL-1 receptor antagonist) prevents symptoms, indicating a crucial role for IL-1 in this disease. OBJECTIVE: To study cytokine responses to cold exposure in monocytes from subjects with FCAS. METHODS: Adherence-enriched monocytes were incubated at 32 degrees C or 37 degrees C. Transcription and release of IL-1beta, IL-6, and TNF-alpha were monitored by quantitative PCR and ELISA. RESULTS: The FCAS monocytes but not control cells responded to 4 h incubation at 32 degrees C with significant secretion of IL-1beta. At 16 h, IL-1beta, IL-6, and TNF-alpha were all significantly elevated in FCAS monocytes at 32 degrees C. Increased cytokine transcription was observed in all monocytes at 4 hours, but at 16 hours it was only seen in FCAS monocytes incubated at 32 degrees C. Incubation at 32 degrees C for as little as 1 hour sufficed to induce measurable IL-1beta release. Caspase-1 inhibitors prevented the cold-induced IL-1beta release, whereas a purinergic antagonist did not. Anakinra had no effect on the early IL-1beta release but significantly reduced the late-phase transcription and release of all cytokines. CONCLUSION: FCAS monocytes respond to mild hypothermia with IL-1beta release, which in turn induces autocrine transcription and secretion of IL-6 and TNF-alpha as well as stimulation of further IL-1beta production. CLINICAL IMPLICATIONS: These results confirm the central role of IL-1beta in FCAS and support the use of IL-1 targeted therapy in these patients.